Prosper: image and robot-guided prostate brachytherapy

Brachytherapy for localized prostate cancer consists in destroying cancer by introducing iodine radioactive seeds into the gland through hollow needles. The planning of the position of the seeds and their introduction into the prostate is based on intra-operative ultrasound (US) imaging. We propose to optimize the global quality of the procedure by: i) using 3D US; ii) enhancing US data with MRI registration; iii) using a specially designed needle-insertion robot, connected to the imaging data. The imaging methods have been successfully tested on patient data while the robot accuracy has been evaluated on a realistic deformable phantom

EAU guidelines on prostate cancer

Objetivos: Presentar un resumen de la versión del 2007 de la guía de la Asociación Europea de Urología (EAU) para el cáncer de próstata (CaP). Métodos: Se realizó por un grupo de trabajo una revisión de los nuevos datos presentes desde 2004 hasta 2007 en la literatura. Las guías han sido actualizadas y el nivel de evidencia/grado de recomendación ha sido añadido al texto basándose en una revisión sistemática de la literatura, que incluía una búsqueda de las bases de datos online y revisiones bibliográficas. Resultados: Una versión completa está disponible en la EAU Office o en www.uroweb.org. El método diagnóstico de elección es la biopsia sistematizada de la próstata bajo control ecográfico. El tratamiento activo es el recomendado en la mayoría de los pacientes con enfermedad localizada y una larga esperanza de vida, siendo la prostatectomía radical superior a la vigilancia ("watchful waiting") en un ensayo randomizado prospectivo. La prostatectomía radical con preservación de bandeletas es la técnica de elección en la enfermedad órgano-confinada; el bloqueo androgénico neoadyuvante no ha demostrado una mejoría en las variables de resultados. La radioterapia debe realizarse con al menos 72 Gy en el CaP de bajo riesgo y con 78 Gy en el de intermedio - alto riesgo. El bloqueo androgénico en monoterapia es el estándar del tratamiento en el CaP metastásico; el bloqueo androgénico intermitente podría ser un tratamiento alternativo en pacientes seleccionados. El seguimiento se basa principalmente en los niveles de PSA y en la anamnesis específica de la enfermedad, estando las pruebas de imagen sólo indicadas cuando aparecen los síntomas. La quimioterapia con docetaxel ha surgido como el tratamiento de referencia para el CaP metastásico hormonorefractario. Conclusiones: El conocimiento en el campo del CaP está rápidamente cambiando. Estas guías de la EAU resumen los hallazgos más recientes y los aplican a la práctica clínica

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate

Biochemical recurrence; Radiotherapy; Prostate adenocarcinomaRecurrència bioquímica; Radioteràpia; Adenocarcinoma de pròstataRecurrencia bioquímica; Radioterapia; Adenocarcinoma de próstataPURPOSE The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.Supported by Cancer Research UK Radiation Research Centre of Excellence at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research (grant A28724) (A.C.T.); Cancer Research UK Programme Grant (C33589/A28284)(A.C.T.); NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research (A.C.T.); grant P50CA09213 from the Prostate Cancer National Institutes of Health Specialized Programs of Research Excellence (A.U.K.); grant PC210066 from the Department of Defense (A.U.K.), the Prostate Cancer Foundation, and the American Society for Radiation Oncology (A.U.K.); and funding from the Chapgier, Bershad, De Silva, and McCarrick Families (A.U.K.)

Medical image computing and computer-aided medical interventions applied to soft tissues. Work in progress in urology

Until recently, Computer-Aided Medical Interventions (CAMI) and Medical Robotics have focused on rigid and non deformable anatomical structures. Nowadays, special attention is paid to soft tissues, raising complex issues due to their mobility and deformation. Mini-invasive digestive surgery was probably one of the first fields where soft tissues were handled through the development of simulators, tracking of anatomical structures and specific assistance robots. However, other clinical domains, for instance urology, are concerned. Indeed, laparoscopic surgery, new tumour destruction techniques (e.g. HIFU, radiofrequency, or cryoablation), increasingly early detection of cancer, and use of interventional and diagnostic imaging modalities, recently opened new challenges to the urologist and scientists involved in CAMI. This resulted in the last five years in a very significant increase of research and developments of computer-aided urology systems. In this paper, we propose a description of the main problems related to computer-aided diagnostic and therapy of soft tissues and give a survey of the different types of assistance offered to the urologist: robotization, image fusion, surgical navigation. Both research projects and operational industrial systems are discussed

MOMP from Campylobacter jejuni is a trimer of 18-stranded β–barrel monomers with a Ca2+ ion bound at the constriction zone

LGMF and SG are funded by EU FP7-PEOPLE-2013-ITN Translocation network Nr. 607694. The research leading to these results was conducted as part of the Translocation consortium (www.translocation.com) and has received support from the Innovative Medicines Initiatives Joint Undertaking under Grant Agreement n°115525, resources which are composed of financial contribution from the European Union’s seventh framework programme (FP7/2007-2013) and EFPIA companies in kind contribution. JHN is Royal Society Wolfson Merit Award holder, Senior Investigator Wellcome Trust (WT100209MA) and Chinese Academy of Science 1000 Talent Scholar.The Gram-negative organism Campylobacter jejuni is the major cause of food poisoning. Unlike Escherichia coli which has two major porins, OmpC and OmpF, C. jejuni has one, termed major outer membrane protein (MOMP) through which nutrients and antibiotics transit. We report the 2.1-Å crystal structure of C. jejuni MOMP expressed in E. coli and a lower resolution but otherwise identical structure purified directly from C. jejuni. The 2.1-Å resolution structure of recombinant MOMP showed that although the protein has timeric arrangement similar to OmpC, it is an18-stranded not 16-stranded β-barrel. The structure has identified a Ca2+ bound at the constriction zone, which molecular dynamics and single channel experiments suggest is functionally significant. The water filled channel of MOMP has a narrow constriction zone and single molecule studies show a monomeric conductivity of 0.7 ± 0.2 nS and a trimeric conductance of 2.2 ± 0.2 nS. The ion neutralizes negative charges at the constriction zone reducing the transverse electric field and reversing ion selectivity. Modelling of the transit of ciprofloxacin, an antibiotic of choice for treating Campylobacter infection, through the pore of MOMP reveals a trajectory that is dependent upon the presence metal ion.Publisher PDFPeer reviewe

Molecular Insights into an Antibiotic Enhancer Action of New Morpholine-Containing 5-Arylideneimidazolones in the Fight against MDR Bacteria

In the search for an effective strategy to overcome antimicrobial resistance, a series of new morpholine-containing 5-arylideneimidazolones differing within either the amine moiety or at position five of imidazolones was explored as potential antibiotic adjuvants against Gram-positive and Gram-negative bacteria. Compounds (7–23) were tested for oxacillin adjuvant properties in the Methicillin-susceptible S. aureus (MSSA) strain ATCC 25923 and Methicillin-resistant S. aureus MRSA 19449. Compounds 14–16 were tested additionally in combination with various antibiotics. Molecular modelling was performed to assess potential mechanism of action. Microdilution and real-time efflux (RTE) assays were carried out in strains of K. aerogenes to determine the potential of compounds 7–23 to block the multidrug efflux pump AcrAB-TolC. Drug-like properties were determined experimentally. Two compounds (10, 15) containing non-condensed aromatic rings, significantly reduced oxacillin MICs in MRSA 19449, while 15 additionally enhanced the effectiveness of ampicillin. Results of molecular modelling confirmed the interaction with the allosteric site of PBP2a as a probable MDR-reversing mechanism. In RTE, the compounds inhibited AcrAB-TolC even to 90% (19). The 4-phenylbenzylidene derivative (15) demonstrated significant MDR-reversal “dual action” for β-lactam antibiotics in MRSA and inhibited AcrAB-TolC in K. aerogenes. 15 displayed also satisfied solubility and safety towards CYP3A4 in vitro

Short Androgen Suppression and Radiation Dose Escalation in Prostate Cancer:12-Year Results of EORTC Trial 22991 in Patients With Localized Intermediate-Risk Disease

The European Organisation for Research and Treatment of Cancer (EORTC) trial 22991 (NCT00021450) showed that 6 months of concomitant and adjuvant androgen suppression (AS) improves event- (EFS, Phoenix) and clinical disease-free survival (DFS) of intermediate- and high-risk localized prostatic carcinoma, treated by external-beam radiotherapy (EBRT) at 70-78 Gy. We report the long-term results in intermediate-risk patients treated with 74 or 78 Gy EBRT, as per current guidelines. Of 819 patients randomly assigned between EBRT or EBRT plus AS started on day 1 of EBRT, 481 entered with intermediate risk (International Union Against Cancer TNM 1997 cT1b-c or T2a with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≤ 7 and PSA ≤ 20 ng/mL, N0M0) and had EBRT planned at 74 (342 patients, 71.1%) or 78 Gy (139 patients, 28.9%). We report the trial primary end point EFS, DFS, distant metastasis-free survival (DMFS), and overall survival (OS) by intention-to-treat stratified by EBRT dose at two-sided α = 5%. At a median follow-up of 12.2 years, 92 of 245 patients and 132 of 236 had EFS events in the EBRT plus AS and EBRT arm, respectively, mostly PSA relapse (48.7%) or death (45.1%). EBRT plus AS improved EFS and DFS (hazard ratio [HR] = 0.53; CI, 0.41 to 0.70; P < .001 and HR = 0.67; CI, 0.49 to 0.90; P = .008). At 10 years, DMFS was 79.3% (CI, 73.4 to 84.0) with EBRT plus AS and 72.7% (CI, 66.2 to 78.2) with EBRT (HR = 0.74; CI, 0.53 to 1.02; P = .065). With 140 deaths (EBRT plus AS: 64; EBRT: 76), 10-year OS was 80.0% (CI, 74.1 to 84.7) with EBRT plus AS and 74.3% (CI, 67.8 to 79.7) with EBRT, but not statistically significantly different (HR = 0.74; CI, 0.53 to 1.04; P = .082). Six months of concomitant and adjuvant AS statistically significantly improves EFS and DFS in intermediate-risk prostatic carcinoma, treated by irradiation at 74 or 78 Gy. The effects on OS and DMFS did not reach statistical significance

International evaluation of the psychometrics of health-related quality of life questionnaires for use among long-term survivors of testicular and prostate cancer

Background: Understanding of the physical, functional and psychosocial health problems and needs of cancer survivors requires cross-national and cross-cultural standardization of health-related quality of life (HRQoL) questionnaires that capture the full range of issues relevant to cancer survivors. To our knowledge, only one study has investigated in a comprehensive way whether a questionnaire used to evaluate HRQoL in cancer patients under active treatment is also reliable and valid when used among (long-term) cancer survivors. In this study we evaluated, in an international context, the psychometrics of HRQoL questionnaires for use among long-term, disease-free, survivors of testicular and prostate cancer. Methods: In this cross-sectional study, we recruited long-term survivors of testicular and prostate cancer from Northern and Southern Europe and from the United Kingdom who had participated in two phase III EORTC clinical trials. Participants completed the SF-36 Health Survey, the EORTC QLQ-C30 questionnaire, the QLQ-PR25 (for prostate cancer) or the QLQ-TC26 (for testicular cancer) questionnaires, and the Impact of Cancer questionnaire. Testicular cancer survivors also completed subscales from the Nordic Questionnaire for Monitoring the Age Diverse Workforce. Results: Two hundred forty-two men (66% response rate) were recruited into the study. The average time since treatment was more than 10 years. Overall, there were few missing questionnaire data, although scales related to sexuality, satisfaction with care and relationship concern